anxiolytics & sedatives

Question 1

barbituates

Answer 1

1st class of drugs developed to tx anxiety- mostly replaced by benzodiazepines

• both drug classes are noted for dependency, both psychological & physical
• CNS depressants=> calming effect, sleep, anesthesia, coma, death
• NO ANALGESIC effect!
• classified by the length of acton
• severe withdrawl ssx- s/t fatal

Question 2

receptor sites for barbs & benzos

Answer 2

-adjacent to GABA site on cell membranes of CNS neurons- increases the affinity of the GABA receptor for GABA= prolonged opening of the CL channels= dec firing opportunity for that neuron
(dec in GABA funx assoc. w/seizures)

Question 3

ultra short acting barbituates

Answer 3

• produce anesthesia w/in 1 min of IV admin
• thiopental/ pentothal- known as “truth serum”, really just disinhibits people, if you don’t want to say something you won’t

Question 4

short acting barbituates

Answer 4

• oral doses produce effects w/in approx. 15-30min, duration of 6-8hrs
• pentobarbital/ nembutal

Question 5

intermediate acting barbituates

Answer 5

• oral admin = 20-40min onset of action, lasts up to 6hs

* butalbital/ fiorinal

Question 6

long acting barbituates

Answer 6

• effect realized in about 1hr, lasts for about 12hrs
• primarily used to tx seizure DO
• phenobarbital/ luminal

Question 7

phenobarbital/ luminal

Answer 7

• most widely used anti-convulsant worldwide
• oldest seizure med still commonly used
• sedative & hypnotic properties- has be replaced by benzodiazepines for this indication

Question 8

benzodiazepines

Answer 8

• most widely used group of anxiolytic drugs
• bind to with high affinity to receptors adjacent to GABA receptors, on cell membrane of CNS- inhances affinity of GABA receptors for endogenous GABA
• opens CL channels= hyperpolarization of neuronal membrane= more difficult to depolarize the nerve cell

Question 9

short acting-benzodiazepines

Answer 9

-generally used for pts with sleep onset insomnia

Question 10

midazolam/ versed

Answer 10

Short acting benzodiazepine
For sedation & anxiety prior to upper GI endoscopy or prior to anesthesia
-potent sedative, hypnotic, anxiolytic, anticonvulsant, skeletal muscle relaxant, amnestic properties
-usu IV, but also syrup for pediatric
-acute management of aggressive, violent or delirious pts
-long-term use for seizure DO is not recommended- development of tolerance, and marked sedation effect

Question 11

long acting benzodiazepines

Answer 11

longer duration of action
for tx of insomnia & anxiety
**esp for tx of seizure DO

Question 12

Examples of long acting benzodiazepines

Answer 12

• Clonazepam/Klonopin
• Diazepam/ Valium
• Clorazepate/ Tranxene

Question 13

Diazepam/ valium

Answer 13

long acting benzodiaepine
used as an anxiolytic, sedative, muscle relaxant, seizure control
MOA- binds to benzodiazepine receptors in CNS- enhances GABA activity
-PO, PR, IV- metabolized in liver to active metabolites, prolongs duration
SE- drowsiness, impaired mentation, tolerance & addiciton. rebound insomnia after discontinuation
**severe withdrawl possible(fatal)
-tx for insomnia has been largely replaced with shorter acting benzo’s

Question 14

benzodiazepine like sedatives

Answer 14

zolpidem/ ambien
zaleplon/sonata
eszopiclone/lunesta
- act to increase GABA receptor affinity for endogenous GABA- do not act on benzo or barb receptor sites

Question 15

zolpidem/ambien

Answer 15

short acting non-benzodiazepine hyponotic
for insomnia
potentiates GABA by binding to GABAa receptors- same location as benzo receptors
works quickly(w/in 15min) w/short half life(2-3hrs)
-does not effectively maintain sleep

Question 16

eszopiclone/lunesta

Answer 16

benzodiazepine-like hypnotic
for insomnia
potentiation of GABA effect on Cl ion channels- does not bind to benzo receptors
PO- rapid onset(15-30min), no evidence of tolerance
SE- impaired mentation prior to sedation, minimal drowsiness upon waking, minimal chx in mentation compared to other benzo’s full side effect profile may not be apparent until 5yr duration of use

Question 17

ramelteon/rozerem

Answer 17

melatonin agonist- sedative hypnotic
for insomnia?
MOA- melatonin receptor agonist, high affinity to melatonin MT1 & MT2 receptors- mimics & enhances the action of endogenous melatonin- associated with maintenance of circadian rhythm
-has shown no measurable affinity to other systems/receptors/transporters/enzymes
-no published studies of effectiveness compared to melatonin supplementation
-available w/out prescription

Question 18

benzodiazepine withdrawl

Answer 18

cluster of ssx that appear when a person who has developed dependence severely reduces/stops intake

• can provoke life threatening symptms. ie. seizures
• rapid onset of ssx with higher dose/longer dependence removal

Question 19

benzodiazepine OD

Answer 19

rare by itself
combined intake with alcohol, barbituates, opioids may cause coma or death
common ssx- CNS depression, signs of intoxication- impaired balance, ataxia, slurred speech
-antidote- flumazenil/romazicon

Question 20

flumazenil/ romazicon

Answer 20

benzodiazepine receptor antagonist
rapidly reverses the effect of benzodiazepines
IV admin only
-rapid onset(1-2min), short half life(1hr)- requires multiple doses to maintain reversal of benzo(esp with OD on long acting benzo’s)
-effective at reversing CNS depression, not so much for respiratory depression
-may cause withdrawal ssx in dependent pts- can cause seizures